Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis

Köfalvi, Attila; Rodrigues, Ricardo J.; Ledent, Catherine; Mackie, Ken; Vizi, E. Sylvester; Cunha, Rodrigo A.; Sperlágh, Beáta

doi:10.1523/jneurosci.4232-04.2005

Cited by 219 publications

(213 citation statements)

References 74 publications

(89 reference statements)

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“…This is in agreement with the findings that D 9 -THC reduced K þ -stimulated, but not basal, glutamate release in striatal slices (Brown et al, 2003). Moreover, at concentrations comparable to those used here (z1e2 mM), WIN 55,212-2 did not affect resting glutamate outflow but reduced, through a CB 1 -mediated mechanism, evoked glutamate release in rat striatal synaptosomes (Kofalvi et al, 2005). It should be noted, however, that the inhibitory effects of CB 1 receptors on glutamate outflow may not be a general mechanism in the brain, since systemic administration of low doses of WIN 55,212-2 has been reported to increase basal extracellular levels of glutamate in the rat cortex (Ferraro et al, 2001).…”

Section: Discussionsupporting

confidence: 92%

“…It should be noted, however, that the inhibitory effects of CB 1 receptors on glutamate outflow may not be a general mechanism in the brain, since systemic administration of low doses of WIN 55,212-2 has been reported to increase basal extracellular levels of glutamate in the rat cortex (Ferraro et al, 2001). To add further complexity to the matter, at concentrations higher than those used by us, the CB 1 receptor antagonist AM251 was found to reduce glutamate release as well (Kofalvi et al, 2005). In spite of these contrasting observations, however, our results confirm the widely accepted notion that cannabinoids exert an inhibitory control on corticostriatal glutamate release.…”

Section: Discussionmentioning

confidence: 65%

“…It should be noted, nonetheless, that the block by AM251 might be not a definite index of a CB 1 -mediated effect. Indeed, a recent report showed that in CB 1 À/À mice, AM251 decreased the inhibitory effect of WIN 55,212-2 on glutamate release (Kofalvi et al, 2005), thus indicating the possible existence of a non-CB 1 , AM251-sensitive cannabinoid receptor. Although the above mentioned findings require caution, it is important to point out that in the striatum of CB 1 À/À mice concentrations of WIN 55,212-2 higher than those effective in the rat striatum or in the mice hippocampus (20 mM) were required to inhibit glutamate release (Kofalvi et al, 2005).…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, a recent report showed that in CB 1 À/À mice, AM251 decreased the inhibitory effect of WIN 55,212-2 on glutamate release (Kofalvi et al, 2005), thus indicating the possible existence of a non-CB 1 , AM251-sensitive cannabinoid receptor. Although the above mentioned findings require caution, it is important to point out that in the striatum of CB 1 À/À mice concentrations of WIN 55,212-2 higher than those effective in the rat striatum or in the mice hippocampus (20 mM) were required to inhibit glutamate release (Kofalvi et al, 2005). Moreover, although WIN 55,212-2 could still stimulate GTP-gS binding in some brain areas from CB 1 -deficient mice, this did not apply to the striatum (Breivogel et al, 2001;Monory et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

“…The ability of CB 1 receptors to inhibit the synaptic release of glutamate in the striatum has been consistently reported (Gerdeman and Lovinger, 2001;Huang et al, 2001). A recent report, which demonstrates the localization of striatal CB 1 receptors in the presynaptic active zone (Kofalvi et al, 2005) has provided an anatomical basis for the inhibitory effects of CB 1 receptor agonists on corticostriatal glutamate release.…”

Section: Introductionmentioning

confidence: 89%

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The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

et al. 2006

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The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum AbstractThe ability of CB 1 receptors to regulate the release of glutamate in the striatum, together with the finding that, in experimental models of Huntington disease (HD), both endocannabinoid levels and CB 1 receptor densities are reduced, has prompted the investigation on the neuroprotective role of the cannabinoids in HD. Quinolinic acid (QA) is an excitotoxin that, when injected in the rat striatum reproduces many features of HD and that acts by stimulating glutamate outflow. The aim of the present study was to test the ability of the cannabinoid receptor agonist WIN 55,212-2 to prevent the effects induced by QA in the rat striatum. In microdialysis experiments, probe perfusion with WIN 55,212-2 significantly and dose-dependently prevented the increase in extracellular glutamate induced by QA. In electrophysiological recordings in corticostriatal slices, the application of WIN 55,212-2 prevented QA-induced reduction of the field potential amplitude. Both effects of WIN 55,212-2 were prevented by the CB 1 receptor antagonist AM 251. In in vivo experiments, intrastriatal WIN 55,212-2 significantly attenuated the striatal damage induced by QA, although no significant effects were observed on a behavioural ground.These data demonstrate that the stimulation of CB 1 receptors might lead to neuroprotective effects against excitotoxic striatal toxicity.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 89%

See 3 more Smart Citations

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

et al. 2006

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Relationship of Type 1 Cannabinoid Receptor Availability in the Human Brain to Novelty-Seeking Temperament

Laere¹,

Goffin²,

Bormans³

et al. 2009

Arch Gen Psychiatry

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Context: Brain neurochemistry can partially account for personality traits as a variance of normal human behavior, as has been demonstrated for monoamine neurotransmission. Positron emission tomography using fluorine 18-labeled MK-9470 now enables quantification of type 1 cannabinoid receptors (CB1R) in the brain.Objective: To investigate whether there is a relationship between human temperament traits and regional cerebral CB1R availability. Participants: Forty-seven nonsmoking, healthy volunteers (paid).Main Outcome Measure: Voxel-based correlation of temperament variables of the inventory with regional CB1R availability.Results: Novelty seeking was inversely correlated with global CB1R availability (r=−0.33, P=.02), with the most significant correlation in the left amygdala (r = −0.41, P =.005). In particular, the subdimension extravagance showed a highly significant inverse correlation to global CB1R availability (r = −0.53, P Ͻ.001), most pronounced in the amygdala, anterior cingulate, parietal cortex, and precuneus. Also, disorderliness was inversely correlated with global CB1R availability (r=−0.31, P=.04).Conclusions: Low baseline cerebral CB1R availability is related to a high novelty-seeking personality, in particular to extravagance, most pronounced in the amygdala. Further investigation of the functional role of the CB1R is warranted in pathological behavior known to be strongly related to novelty seeking, such as addiction and eating disorders.

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Non‐Dopaminergic Approaches to the Treatment of Parkinson's Disease

Fox

Brotchie

2011

Parkinson's Disease

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Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis

Cited by 219 publications

References 74 publications

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

Relationship of Type 1 Cannabinoid Receptor Availability in the Human Brain to Novelty-Seeking Temperament

Non‐Dopaminergic Approaches to the Treatment of Parkinson's Disease

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